Nanobiotix SA (NBTX) 2024 Q4 法說會逐字稿

Good day, and welcome to the Nanobiotix business update and full-year 2024 financial results conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

大家好，歡迎參加 Nanobiotix 業務更新和 2024 年全年財務業績電話會議。（操作員指示）請注意，今天的會議正在錄音。

At this point, I would turn the call over to Craig West, Senior Vice President of Investor Relations of Nanobiotix. Please go ahead.

現在，我將把電話轉給 Nanobiotix 投資者關係資深副總裁 Craig West。請繼續。

Thank you. Good afternoon and good morning, and welcome to the Nanobiotix conference call to discuss our full-year 2024 financial and operational results. Joining me on the call today are Laurent Levy, Co-Founder and Chief Executive Officer; and Bart van Rhijn, Chief Financial and Business Officer. As a reminder, today's call is being webcast and will be available on our website for replay.

謝謝。下午好，早上好，歡迎參加 Nanobiotix 電話會議，討論我們 2024 年全年財務和營運業績。今天與我一起參加電話會議的還有共同創辦人兼執行長 Laurent Levy 和財務與業務長 Bart van Rhijn。提醒一下，今天的電話會議正在進行網路直播，您可以在我們的網站上重播。

On the next slide, slide 2, I would like to remind you that this call will include forward-looking statements, which may include statements regarding the progress, success, and timing of our ongoing and planned clinical trials, collaborations, regulatory filings, dates of presentation, and future research and development efforts, amongst other things. These forward-looking statements are based on current information, assumptions, and expectations that are subject to change. They are subject to significant risks and uncertainties that could cause the company's actual results to differ materially from our current expectations.

在下一張投影片（投影片 2）中，我想提醒您，本次電話會議將包括前瞻性陳述，其中可能包括有關我們正在進行和計劃中的臨床試驗、合作、監管備案、演示日期和未來研究和開發工作的進展、成功和時間安排的陳述等。這些前瞻性陳述基於當前資訊、假設和預期，可能會發生變化。它們面臨重大風險和不確定性，可能導致公司的實際結果與我們目前的預期有重大差異。

Accordingly, you are cautioned not to place undue reliance on forward-looking statements. Please review the full description of risk factors that can be found in the documents we filed with the AMF in France and SEC in the United States, which are available in the Investor Relations section of our website, along with the press release issued yesterday highlighting our corporate and financial results for the period.

因此，請注意不要過度依賴前瞻性陳述。請查看我們向法國金融市場監管機構 (AMF) 和美國證券交易委員會 (SEC) 提交的文件中所包含的風險因素的完整描述，這些文件可在我們網站的「投資者關係」部分找到，同時也請查看昨天發布的新聞稿，其中重點介紹了我們該期間的公司和財務業績。

In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, Nanobiotix undertakes no obligation to update them to reflect subsequent events or future circumstances.

此外，任何前瞻性陳述僅代表我們截至今天的觀點，不應被視為代表我們在任何後續日期的觀點。雖然我們可能選擇在未來某個時間點更新這些前瞻性陳述，但 Nanobiotix 不承擔更新它們以反映後續事件或未來情況的義務。

With that said, I'd like to turn the call over to Laurent. Please go ahead.

話雖如此，我想把電話轉給 Laurent。請繼續。

Thank you, Craig, and welcome, everyone. Today, we're going to talk about the progress we've been making with NBTXR3 or JNJ-1900. And also, we'll give you some financial highlights and operational highlights for '24 and '25. And we'll end this call with a Q&A session.

謝謝你，克雷格，歡迎大家。今天，我們將討論 NBTXR3 或 JNJ-1900 所取得的進展。此外，我們還將為您提供 24 年和 25 年的一些財務亮點和營運亮點。我們將以問答環節結束本次通話。

We have made very good progress toward our pathway to sustainability and growth, and starting by continuing pushing and developing this collaboration with J&J. In '23, we've been signing this $2.6 billion deal plus royalties with J&J and now pushing into different direction and different indication. If you think about just the two first indications in lung cancer and head and neck cancer, those two first only could represent over 100,000 patients addressable in the US and EU5 alone, which could lead to a potential $10 billion market. As you will see, we have many things ongoing, and this collaboration is progressing well.

我們在永續發展和成長的道路上取得了非常好的進展，首先是繼續推動和發展與強生公司的合作。23 年，我們與強生公司簽署了價值 26 億美元的協議，外加特許權使用費，現在我們正朝著不同的方向和不同的適應症邁進。如果只考慮肺癌和頭頸癌這兩個首批適應症，那麼僅在美國和歐盟五國，這兩個首批適應症就可能涉及超過 10 萬名患者，這可能會帶來 100 億美元的潛在市場。正如您所看到的，我們有很多事情正在進行中，而且這次合作進展順利。

But it's not the only thing that would lead us to sustainability. There is also the new platform we are developing. And this year, we've been launching our new platform, first-in-class product with Curadigm. We will talk about that a bit later.

但這並不是引領我們走向永續發展的唯一因素。還有我們正在開發的新平台。今年，我們與 Curadigm 合作推出了我們的新平台和一流的產品。我們稍後會討論這個問題。

But first, let's move to next slide and see how do we tend to address one of the largest untapped markets in oncology. Slide 6, you can see our pipeline. And as you will remember, NBTXR3, our product, is a product that is very versatile, a product that is tumor agnostic, patient agnostic, and target agnostic, which means that we could literally combine that in many indications in oncology, as you can see in our pipeline. So we've been progressing a lot this pipeline this year in different indications, including two very important ones: the NANORAY-312, which concern elderly patient in head and neck that are frail and ineligible to cisplatin; but also the lung stage 3 program that J&J started this year.

但首先，讓我們進入下一張投影片，看看我們如何解決腫瘤學中最大的未開發市場之一。投影片 6，您可以看到我們的管道。您會記得，我們​​的產品 NBTXR3 用途非常廣泛，它與腫瘤、患者和標靶無關，這意味著我們可以將其結合到腫瘤學的許多適應症中，正如您在我們的產品線中看到的那樣。因此，我們今年在不同適應症方面取得了很大進展，其中包括兩個非常重要的適應症：NANORAY-312，針對體質虛弱且不適合使用順鉑的老年頭頸部患者；以及強生公司今年啟動的肺癌 3 期計畫。

Let's move to the key development we've been doing, starting with NANORAY-312. This is our pivotal Phase 3 study in locally advanced head and neck cancer. It is a global study, 500 patients randomized one-to-one. What we've been doing in '24 is first aligning on the transfer to J&J of this program. And we did that midstream of the development of the NANORAY-312.

讓我們開始討論我們一直在進行的關鍵開發，從 NANORAY-312 開始。這是我們針對局部晚期頭頸癌的關鍵性第 3 期研究。這是一項全球性研究，500名患者一對一隨機分組。我們在 24 年所做的工作首先是協調將該專案轉移給強生公司。我們在 NANORAY-312 的開發過程中完成了這項工作。

Why we did it? Because we thought it was the best thing possible to do with this study. Rather than waiting the final data before transferring, which would have caused some delay post-result, we said that it would be much better to do it now in order for J&J to be ready, assuming the data are positive, to push the return and start registration of the product. We expect to complete this transfer around Q3 of this year. So that's for the NANORAY-312, which is progressing and now being transferred to J&J.

我們為什麼這麼做？因為我們認為這是這項研究所能做的最好的事。我們說，與其等待最終數據出來後再轉移，因為這會導致結果出來後出現一些延遲，不如現在就轉移，這樣強生公司就可以做好準備，假設數據是積極的，就可以推動回報並開始產品註冊。我們預計此次轉移將在今年第三季左右完成。這就是 NANORAY-312 的情況，該研究正在進行中，目前正在轉移到強生公司。

On the other side, J&J has started a new trial named CONVERGE. It is a randomized Phase 2 study in unresectable stage 3 lung cancer. And the first patient has been dosed in January this year. And this trial progressed quite well.

另一邊，強生公司啟動了一項名為CONVERGE的新試驗。這是一項針對不可切除的 3 期肺癌的隨機 2 期研究。首位患者已於今年1月接受治療。這次試驗進展相當順利。

Moving to next slide. Those are not the two only development or clinical development that have progressed. We also have early-stage study that are progressing across solid tumor. Let's start with head and neck recurrent and recurrent metastatic cancer patients that are eligible to PD-1.

移至下一張投影片。這並不是僅有的兩個取得進展的開發或臨床開發。我們也進行了針對實體瘤的早期研究。讓我們從適合 PD-1 治療的頭頸部復發性和復發性轉移性癌症患者開始。

So of Phase 1 Study 1100, I've been showing last year some positive data, showing safety, feasibility, and also very good disease control and tumor response. And we expect to give this year an update on this trial, both on patients that are first-line PD-1, but also refractory PD-1 on the completion of these two cohorts.

因此，對於第一階段研究 1100，我去年展示了一些積極的數據，顯示了安全性、可行性以及非常好的疾病控制和腫瘤反應。我們預計今年將更新這項試驗的最新情況，包括針對第一線 PD-1 患者以及難治性 PD-1 患者完成這兩組試驗後的情況。

We've been also progressing in pancreatic cancer. That's one of the trials we are doing with MD Anderson Cancer Center. It is about patients that are locally advanced or borderline resectable. We've been completing the Phase 1 and got some really encouraging outcome in terms of safety profile of the product, but also in terms of efficacy.

我們在胰臟癌治療方面也取得了進展。這是我們與 MD 安德森癌症中心合作進行的試驗之一。它適用於局部晚期或邊緣可切除的患者。我們已經完成了第一階段，並在產品的安全性和功效方面取得了一些非常令人鼓舞的結果。

And as we've seen such a good result for the Phase 1, we decided with MDA to expand into a new cohort, which this time will be the same treatment within the standard of care, meaning radiation plus chemo plus nano particle for pancreatic locally advanced cancer patients. This second cohort has started and recruiting well. We should expect also this year to get a result from the escalation part and the expansion part of the trial before the summer.

由於我們看到第一階段的良好結果，我們決定與 MDA 合作擴展到新的隊列，這次將採用標準護理內的相同治療方法，即針對胰腺局部晚期癌症患者的放療加化療加奈米顆粒治療。第二批學員已開始訓練，招募工作進展順利。我們也應該期望今年夏天之前就能從試驗的升級部分和擴展部分得到結果。

In lung cancer, we recently published some data coming also from MD Anderson Cancer Center. They have completed the dose escalation part of a Phase 1 in non-small cell lung cancer that already received some previous treatment and that are eligible for re-irradiation. So the data were really good in terms of safety and feasibility, again, very consistent versus other trials we've been showing.

在肺癌方面，我們最近發布了一些來自 MD 安德森癌症中心的數據。他們已經完成了非小細胞肺癌第一階段的劑量遞增部分，該癌症患者之前已經接受過一些治療，並且有資格再次接受放射治療。因此，就安全性和可行性而言，數據確實非常好，與我們展示的其他試驗相比非常一致。

And we start to see even early some very interesting sign of efficacy, meaning local control of the tumor, which is essential for those patients. So as you can see, we have been progressing the pipeline and will continue as we expect many more clinical data coming this year.

我們甚至在早期就開始看到一些非常有趣的療效跡象，即腫瘤的局部控制，這對這些患者來說至關重要。正如您所看到的，我們一直在推進這一進程，並將繼續下去，因為我們預計今年將有更多的臨床數據。

In parallel to NBTXR3 or JNJ-1900, we've been launched Curadigm, our fully owned next-generation nanotherapeutic platform. This is based on nanoparticle and nanophysics. And again, something that we expect to be useful for many, many patients, millions of patients, but not only for one indication or one therapeutic area. It is something that we expect to be used in many therapeutic areas in combination with many types of product.

與 NBTXR3 或 JNJ-1900 同時推出的是 Curadigm，這是我們完全擁有的下一代奈米治療平台。這是基於奈米粒子和奈米物理學。再次強調，我們期望某些東西對很多很多患者，數百萬患者都有用，但不僅僅是針對一種適應症或一個治療領域。我們希望它能與多種類型的產品結合用於許多治療領域。

So as you may remember, those are nanoparticles that are designed to temporarily occupy the liver. And while the liver is busy with those particles, when you inject something else in the patient, then the liver accumulation will be decreased and, to a certain extent, will completely change the bioavailability of the second product that you inject. So this has a strong potential to increase efficacy or decrease toxicity of existing products. But where we think it could be really, really big is because we can create all new therapy with a unique competitive positioning, something that we work internally to start building our own pipeline.

您可能還記得，這些是旨在暫時佔據肝臟的奈米粒子。當肝臟忙於處理這些顆粒時，當您在患者體內註射其他物質時，肝臟的蓄積就會減少，並且在一定程度上會徹底改變您注射的第二種產品的生物利用度。因此，這很有可能提高現有產品的功效或降低其毒性。但我們認為它真正能夠發揮巨大作用的原因是，我們可以創造出具有獨特競爭定位的全新療法，這是我們內部努力開始建立自己的管道的事情。

But as I mentioned, this is a technology that could be widely applicable, and therefore, this is an ideal candidate or candidates, I should say, to make potential multiple partnership. And that's a strong activity we are leading this year, talking to biotech and pharma industry.

但正如我所提到的，這是一項可以廣泛應用的技術，因此，我應該說，這是建立潛在多重合作關係的理想候選人。這是我們今年領導的一項重要活動，與生物技術和製藥行業進行交流。

On the top of progressing our collaboration and platform development, we also have added two new Board observers to the Nanobiotix Board, Margaret and Anat, and we'd like to welcome them for the contribution. Also, they already have brought to the company and the future contribution. We intend to confirm this observer and make them full member at the next General Assembly.

除了推動合作和平台開發之外，我們還為 Nanobiotix 董事會增加了兩名新的董事會觀察員，Margaret 和 Anat，我們歡迎他們做出貢獻。而且他們已經為公司以及未來做出了貢獻。我們打算在下次大會上確認該觀察員並使其成為正式成員。

That's it for this party. And I'm now going to give the mic to Bart to give you some operational and financial highlight.

這次聚會就到這裡了。現在我將把麥克風交給巴特，讓他向大家介紹一些營運和財務方面的亮點。

Thank you, Laurent. Good morning and good afternoon, everyone.

謝謝你，洛朗。大家早安，下午好。

Moving to the next slide. As Laurent mentioned earlier, Nanobiotix has had an extremely productive year, and we've been executing our disciplined financial strategy to move the company towards long-term sustainability and growth. Subsequent to our progress in 2023, in which we signed the license agreement with Johnson & Johnson, and completed the follow-on offering, recent activities include the receipt of the first milestone payment in May 2024, when we received the $20 million payment related to NANORAY-312 progress.

移至下一張投影片。正如 Laurent 之前提到的，Nanobiotix 今年取得了極其豐碩的成果，我們一直在執行嚴謹的財務策略，推動公司實現長期永續發展和成長。繼 2023 年我們與強生公司簽署許可協議並完成後續發行之後，最近的活動包括 2024 年 5 月收到第一筆里程碑付款，當時我們收到了與 NANORAY-312 進展相關的 2000 萬美元付款。

And continuing this execution, we announced last month the signing of an amendment to the global licensing agreement for NBTXR3. This amendment has several important provisions, including removing the vast majority of the Nanobiotix funding obligation for NANORAY-312, releasing J&J from select future potential milestone payments, and safeguarding Nanobiotix's path to sustainable cash flow through hundreds of millions in potential milestone payments related to lead programs expected in the coming years. As a result of these changes to the license agreement, we have extended our cash runway to mid-2026, and not to be missed, these changes should result in a meaningful reduction in cash burn beyond mid-2026, as the full cost of a Phase 3 study will no longer be reflected in our financials.

為了繼續執行這項計劃，我們上個月宣布簽署了 NBTXR3 全球授權協議的修訂版。該修正案包含幾項重要條款，包括取消 Nanobiotix 對 NANORAY-312 的絕大部分資助義務、免除強生公司未來部分潛在里程碑付款，以及通過預計未來幾年與主要項目相關的數億美元潛在里程碑付款來保障 Nanobiotix 實現可持續現金流的道路。由於這些授權協議的變化，我們將現金流延長至 2026 年中期，不容錯過的是，這些變化應該會導致 2026 年中期以後的現金消耗顯著​​減少，因為第三階段研究的全部成本將不再反映在我們的財務狀況中。

And we're not done. We are continuing to actively explore further financing options, preferably non-dilutive, to extend cash visibility into 2027. This is rooted in the belief that our first platform provides a path for Nanobiotix to reach financial stability in the next few years.

我們還沒完成。我們將繼續積極探索進一步的融資選擇，最好是非稀釋性的，以將現金可見度延長至 2027 年。這是因為我們堅信我們的第一個平台將為 Nanobiotix 在未來幾年實現財務穩定提供一條道路。

As we advance to the next slide, we show here the elements of the amended agreement over time. We can share with you what has transpired so far, as well as our outlook, should data readouts and regulatory approvals come in positive. The left column represents elements of the agreement that occurred already or are ongoing. This includes the $80 million already received made up of the upfront equity and the first milestone I mentioned previously. There are many elements of the agreement ongoing, such as tech transfer, product supply, J&J investing in duplication of our manufacturing capabilities, and starting the randomized CONVERGE study in non-small cell lung cancer.

當我們進入下一張投影片時，我們在這裡展示了修訂後的協議隨時間的變化。如果數據讀數和監管部門批准結果呈積極態勢，我們可以與您分享迄今為止發生的事情以及我們的展望。左欄代表已經發生或正在進行的協議要素。這包括已經收到的 8000 萬美元，由前期股權和我之前提到的第一個里程碑組成。該協議的許多內容正在進行中，例如技術轉移、產品供應、強生投資複製我們的製造能力以及啟動非小細胞肺癌的隨機 CONVERGE 研究。

In the middle, you can see that there's $200 million plus of medium-term milestones that we expect in the next two to three years. This should lead to a sustainably financed company with the increased commitments from J&J.

在中間，您可以看到我們預計未來兩到三年內將實現 2 億美元以上的中期里程碑。隨著強生公司承諾的增加，這將使公司獲得可持續的融資。

When we look at the right-hand side of the slide, we can see that we maintain the royalties. We maintain the $220 million per new indication developed by Nanobiotix, which would require funding by Nanobiotix, as well as more than $2.3 billion relating to long-term milestones of the ongoing programs, development, and regulatory milestones on potential additional indications, sales milestones that are indication agnostic, as well as the LianBio milestones for Greater China region. I'll describe these more in a moment. The settlement of these items allows Nano to focus on supporting J&J regarding the operational success of NANORAY-312 as reflected in the amendment.

當我們查看投影片的右側時，我們可以看到我們保留了版稅。我們維持 Nanobiotix 開發的每種新適應症 2.2 億美元的投資，這需要 Nanobiotix 的資金支持，此外還有超過 23 億美元的資金用於正在進行的項目的長期里程碑、潛在的額外適應症的開發和監管里程碑、與適應症無關的銷售里程碑以及大中華區的 LianBio 里程碑。我稍後會更詳細地描述這些。這些事項的解決使 Nano 能夠專注於支持強生在修正案中體現的 NANORAY-312 的營運成功。

As we turn to the next slide, I wanted to share a recap of the overall structure post the amendment. We've presented this before, and these are post-amendment numbers. As I already indicated, royalties have not changed, and the $105 million in total has been removed from the first and third bucket from a milestone perspective. The first bucket now reaches up to $1.77 billion, and the third bucket, which was the LianBio bucket, now Janssen bucket, reaches up to $165 million versus $205 million prior related to the Greater China region. In total, the agreement and rights assignment represent a potential of $2.6 billion in milestones with potential for additional milestones from indications we may develop and fund, and we'll receive tiered royalties from the low teens to low 20s as percent of sales.

當我們翻到下一張投影片時，我想分享一下修訂後的整體結構回顧。我們之前已經提出過這一點，這些是修訂後的數字。正如我已經指出的，版稅沒有改變，從里程碑的角度來看，總計 1.05 億美元已從第三個桶中移除。第一個桶現在已達到 17.7 億美元，第三個桶（即聯拓生物桶，現為楊森桶）已達到 1.65 億美元，而先前與大中華區相關的桶為 2.05 億美元。總體而言，該協議和權利轉讓代表著潛在的 26 億美元里程碑，並且我們可能從可能開發和資助的適應症中獲得更多里程碑，並且我們將獲得從銷售額的百分之十幾到百分之二十幾的分級特許權使用費。

Now, let's turn our attention to the full-year 2024 financial highlights on the next slide. Negative revenue of EUR7.2 million was recognized in 2024 compared to EUR36.2 million for the year ended December 31, 2023. Significant revenue was recorded in 2023 in connection with the execution of the license agreement with Janssen, as well as the recognition of the NANORAY-312 development milestone.

現在，讓我們將注意力轉向下一張投影片上的 2024 年全年財務亮點。2024 年確認的負收入為 720 萬歐元，而截至 2023 年 12 月 31 日的年度為 3,620 萬歐元。2023 年，隨著與 Janssen 簽訂授權協議以及 NANORAY-312 開發里程碑的認可，公司取得了可觀的收入。

The negative revenue impact recognized in 2024 results from the transfer of NANORAY-312 study sponsorship to Janssen signed at the end of 2024, which amounts to negative EUR19.3 million revenue impact, which is driven by a one-time recognition of a net liability towards Janssen to reflect this new situation. This net liability is made up of the refund obligation the company has towards Janssen regarding NANORAY-312 total remaining costs that will remain with the company, which is offset by residual contract liability and R&D services recognized in 2024.

2024 年確認的負面收入影響是由於 2024 年底簽署的 NANORAY-312 研究贊助轉移給楊森，這相當於負 1930 萬歐元的收入影響，這是由於一次性確認對楊森的淨負債以反映這一新情況。此淨負債由公司對 Janssen 就 NANORAY-312 剩餘總成本應承擔的退款義務組成，該義務由 2024 年確認的剩餘合約負債和研發服務抵銷。

This net liability was recognized at the time of the execution of the amendment and is a result of the application of IFRS 15 revenue recognition accounting treatment, which generates a cumulative negative catch-up. To be clear, this negative revenue amount is a non-cash item and, therefore, does not impact Nano's cash position.

此淨負債是在執行修訂時確認的，是應用 IFRS 15 收入確認會計處理的結果，產生了累計負追補。需要明確的是，這筆負收入金額是非現金項目，因此不會影響 Nano 的現金狀況。

This one-off negative impact is partially offset by other revenues recognized in 2024 that conversely do positively impact our cash position, including sales of clinical products and supplies for EUR5.9 million, technology transfer services built to Janssen for EUR1.8 million, and research tax credits for EUR3.3 million.

這一一次性負面影響被 2024 年確認的其他收入部分抵消，這些收入反而對我們的現金狀況產生了積極影響，包括 590 萬歐元的臨床產品和用品銷售額、180 萬歐元的向 Janssen 提供的技術轉移服務以及 330 萬歐元的研究稅收抵免。

R&D expenses consist primarily of preclinical, clinical, and manufacturing expenses related to development of NBTXR3 and totals EUR40.5 million for the 12-month period ended December 31, 2024, as compared to EUR38.4 million for the 12 months ended December 31, 2023. A 5% increase in net R&D expenses was primarily due to an increase of clinical development activities driven by the cost related to NANORAY-312 and the Phase 1 multi-cohort trial of RT-activated NBTXR3, followed by anti-PD-1 checkpoint inhibitors, also known as Study 1100, as well as the full-year impact of R&D positions that were recruited in 2023.

研發費用主要包括與 NBTXR3 開發相關的臨床前、臨床和製造費用，截至 2024 年 12 月 31 日的 12 個月總計 4,050 萬歐元，而截至 2023 年 12 月 31 日的 12 個月總計 3,840 萬歐元。淨研發費用增加 5% 主要是由於與 NANORAY-312 和 RT 激活的 NBTXR3 的 1 期多隊列試驗相關的成本推動的臨床開發活動增加，隨後是抗 PD-1 檢查點抑製劑（也稱為研究 1100），以及 2023 年招聘的研發職位對全年的影響。

When we turn our attention to selling, general and administrative expenses, these were EUR20.5 million for the year ended December 31, 2024, compared to EUR22 million for the year ended December 31, 2023. The 7% year-over-year decrease is mainly due to one-off fees incurred in 2023, consisting of license agreement execution and equity issuance-related legal expenses, next to one-off fees paid to a financial advisor for EUR1.9 million in total.

當我們將注意力轉向銷售、一般和行政費用時，截至 2024 年 12 月 31 日止年度的銷售、一般和行政費用為 2050 萬歐元，而截至 2023 年 12 月 31 日止年度的銷售、一般和行政費用為 2200 萬歐元。年比下降 7% 主要是由於 2023 年產生的一次性費用，包括許可協議執行和股票發行相關的法律費用，以及支付給財務顧問的一次性費用總計 190 萬歐元。

Net loss attributable to shareholders was EUR68.1 million, a year-over-year increase of 72%, or EUR1.44 per share for the 12-month period ended December 31, 2024, which is primarily attributable to the one-off negative revenue recognition accounting impact, which again was a non-cash item. This compares to a net loss of EUR39.7 million, or EUR1.08 per share for the year ended December 31, 2023.

截至 2024 年 12 月 31 日的 12 個月期間，歸屬於股東的淨虧損為 6,810 萬歐元，年成長 72%，即每股 1.44 歐元，這主要歸因於一次性負面收入確認會計影響，這又是非現金項目。相較之下，截至 2023 年 12 月 31 日的年度淨虧損為 3,970 萬歐元，即每股 1.08 歐元。

As we look at cash and cash equivalents, as of December 31, 2024, Nanobiotix had EUR49.7 million in cash and cash equivalents, compared to EUR75.3 million as of December 31, 2023. Based on the current operating plan and financial projections, Nanobiotix anticipates that the cash and cash equivalents of EUR49.7 million as of December 31, 2024, will fund its operations into mid-2026.

從現金和現金等價物來看，截至 2024 年 12 月 31 日，Nanobiotix 擁有 4,970 萬歐元現金和現金等價物，而截至 2023 年 12 月 31 日為 7,530 萬歐元。根據目前的營運計畫和財務預測，Nanobiotix 預計截至 2024 年 12 月 31 日的現金和現金等價物為 4,970 萬歐元，將為其到 2026 年中期的營運提供資金。

To conclude, we have a disciplined capital allocation approach, and our recently amended licensing deal arrives at a structure that puts the company on a path towards a sustainably financed company, subject to milestones or regulatory approvals coming in positive. We are very excited regarding the potential of NBTXR3 or JNJ-1900 and are focused on bringing this first-in-class radio enhancer to the market together with our partner.

總而言之，我們有一個嚴謹的資本配置方法，我們最近修改的許可協議形成了一種結構，使公司走上了可持續融資的道路，但前提是取得里程碑或獲得監管部門的批准。我們對 NBTXR3 或 JNJ-1900 的潛力感到非常興奮，並致力於與我們的合作夥伴一起將這款一流的無線電增強器推向市場。

And now, I will turn the call back to Laurent. Laurent?

現在，我將把電話轉回給 Laurent。洛朗？

Thank you, Bart. Let's see what's coming in the next 18 months for Nanobiotix.

謝謝你，巴特。讓我們看看 Nanobiotix 在未來 18 個月內會有什麼發展。

As you can see, on slide 16, we expect to get a very important milestone next year, namely the end of recruitment of the ongoing Phase 3 in head and neck. That should lead, assuming the data are positive, to potential registration. There's also the stage 3 randomised Phase 2 in non-small cell and cancer that J&J has started that should start reading in the not-too-distant future.

如您所見，在第 16 張投影片上，我們預計明年將取得一個非常重要的里程碑，即正在進行的頭頸部第 3 階段招募的結束。假設數據是積極的，這應該會導致潛在的註冊。強生公司也啟動了針對非小細胞和癌症的 3 期隨機 2 期臨床試驗，預計在不久的將來即可開始閱讀。

But what's coming for this year is more data. And starting with the head and neck refractory patients that are eligible to PD-1, either as a first-line or second-line or third-line treatment, and we expect to get data on those two cohorts by the end of '25. The non-small cell and cancer trial coming from MDA has been published just a few days ago, but there will be more coming from the MD Anderson Cancer Center, where we'll have the full data of the pancreatic cancer Phase 1 trial that should be published before mid-year this year.

但今年將會有更多數據。首先從適合 PD-1 治療的頭頸部難治性患者開始，無論是作為第一線、二線或三線治療，我們預計到 25 年底將獲得這兩組患者的數據。來自 MDA 的非小細胞和癌症試驗幾天前剛發布，但 MD 安德森癌症中心還將發布更多內容，我們將獲得胰腺癌第一階段試驗的完整數據，該數據將於今年年中之前發布。

And for the second part of the year, we're waiting also for the first data coming from the last cohort, coming from the 1100 trial, which are patients that received multiple IO treatment and some others that got refractory. And then we have injected our product plus radiation continuation of PD-1 to see if we can rescue those patients. And most of the patients here have been melanoma patients, and we're really eager to present this data.

對於今年下半年，我們還在等待來自最後一批患者的首批數據，這群患者來自 1100 例試驗，這些患者接受了多次 IO 治療，還有一些患者出現難治性治療。然後我們注射了我們的產品加上 PD-1 的放射延續，看看我們是否可以拯救這些患者。這裡的大多數患者都是黑色素瘤患者，我們非常渴望展示這些數據。

And finally, coming from MD again, the esophageal Phase 1 first data, we will start updating this program by the end of this year. So as you can see, there will be a lot to say from now to the end of the year while waiting some of the key important milestones in locally advanced head and neck cancer Phase 3 or lung stage 3 randomized Phase 2 run by J&J.

最後，再次來自 MD 的食道第一階段首批數據，我們將在今年年底開始更新該計劃。因此，正如您所看到的，從現在到年底，在等待強​​生公司開展的局部晚期頭頸癌 3 期或肺癌 3 期隨機 2 期的一些關鍵重要里程碑的同時，還有很多話要說。

In a nutshell, for today, what we would like to take away is, first of all, we're moving forward with the partnership with J&J. It does evolve and progressing really well. We have continued also to show the potential and opening the potential of NBTXR3 in multiple indication.

簡而言之，今天我們首先要說的是，我們正在推動與強生公司的合作。它確實發展並進步得很好。我們也將繼續展示並挖掘 NBTXR3 在多種適應症中的潛力。

This year -- or last year, sorry, has been a good time to introduce our new platform, Curadigm. And equally importantly, not only we are growing our different option to develop product to help patients, but we're really moving toward financial sustainability and growth for the company. And last year, we've been clearly strengthened our financial position. And finally, we're coming with end of the year, where we expect many more clinical readouts and more to come.

今年——或者抱歉，是去年——是推出我們的新平台 Curadigm 的好時機。同樣重要的是，我們不僅在開發產品來幫助患者方面提供不同的選擇，而且我們正在真正朝著公司的財務可持續性和成長邁進。去年，我們的財務狀況明顯增強。最後，隨著年底的到來，我們期待更多的臨床讀數和更多內容。

So with that, I'll conclude the first part, and we'll open the session for Q&A.

因此，我將結束第一部分，然後我們將開始問答環節。

(Operator Instructions) Jonathan Chang, Leerink Partners.

（操作員指示）Jonathan Chang，Leerink Partners。

Hi. Good morning. This is Yen-Der Li on for Jonathan Chang. Thanks for taking my questions. So I have two questions. So the first one, could you provide more details on the recently initiated Phase 2 CONVERGE study by J&J? Specifically, when can we expect to see the initial data? And what factor gives you confidence in the study's potential for success? Thank you.

你好。早安.這是 Yen-Der Li 代替 Jonathan Chang 上場。感謝您回答我的問題。我有兩個問題。那麼第一個問題，您能否提供更多有關強生公司最近啟動的第二階段 CONVERGE 研究的細節？具體來說，我們什麼時候可以看到初始數據？哪些因素讓您對這項研究的成功潛力充滿信心？謝謝。

Thank you. Unfortunately, for now, we can't tell anything more that the trial has started and progressing well, and we'll come to our partner to define when will be the first readout of this trial.

謝謝。不幸的是，目前我們無法透露更多有關試驗已經開始和進展順利的消息，我們將與我們的合作夥伴確定何時首次公佈該試驗的結果。

Now, concerning the other part of the question about why this population and what should we expect and what do we think NBTXR3 could make a difference here, I think it's in going to the continuation of having consistently showing very good local control induced by our product when combined with radiation. And in this specific population of locally advanced non-small cell lung cancer, so stage 3 patient and resectable, that usually get the PACIFIC regimen, which is radiation, chemo, and followed by PD-L1, assuming they did not progress in between, there's still a low bar in terms of local response. And more generally in oncology, when you have good local response for locally advanced cancer patients without met, then this translates into PFS and OS, what we have seen in head and neck, what we see in other indications.

現在，關於問題的另一部分，為什麼這個人群以及我們應該期待什麼以及我們認為 NBTXR3 可以在這裡產生什麼影響，我認為這將持續顯示出我們的產品與放射相結合時誘導的非常好的局部控制。在局部晚期非小細胞肺癌這一特定人群中，即 3 期且可切除的患者，通常會接受 PACIFIC 方案，即放療、化療，然後進行 PD-L1 治療，假設他們在此期間沒有進展，那麼在局部反應方面仍然有一個較低的標準。更普遍的是，在腫瘤學中，當對未達到治療標準的局部晚期癌症患者有良好的局部反應時，這轉化為 PFS 和 OS，這是我們在頭頸部和其他適應症中看到的。

So clearly, the point here is to bring much better local control to those patients. So that's the context of this randomized trial. Now, what we start seeing across different indications, as I mentioned, show already a good local control brought by NBTXR3, and we think the recent data generated by MDA is also a good sign of what could happen in the CONVERGE study.

因此顯然，這裡的重點是為這些患者帶來更好的局部控制。這就是這次隨機試驗的背景。現在，正如我所提到的，我們開始看到不同適應症的結果已經表明 NBTXR3 帶來了良好的局部控制，我們認為 MDA 生成的最新數據也是 CONVERGE 研究中可能出現的結果的一個好兆頭。

Understood. Thank you. Very helpful. And my second question is about the upcoming pancreatic cancer data presentation. We're curious, how will the information presented there be different from the press release last year. And if the results are promising, what would the next step be for NBTXR3 in this indication? Thank you.

明白了。謝謝。非常有幫助。我的第二個問題是關於即將舉行的胰臟癌數據報告。我們很好奇，那裡呈現的資訊與去年的新聞稿有何不同。如果結果令人鼓舞，那麼 NBTXR3 下一步將如何應對這種情況？謝謝。

Thank you. So end of last year, we announced the completion of the Phase 1 that was including an escalation part and an expansion part and just gave the top-line overall survival for the patient. So what we should expect as a readout for this is the full data, including efficacy, safety, some of the potential biomarker that have been used, so that MDA is working on that aspect right now.

謝謝。因此，去年年底，我們宣布完成第一階段，其中包括升級部分和擴展部分，並為患者提供了最高總體存活率。因此，我們應該期待的是完整的數據讀數，包括功效、安全性、一些已使用的潛在生物標記物，因此 MDA 目前正在研究這方面的問題。

There's already a next step that has started when we announced that FDA approved an amendment to the protocol that is adding a new cohort, and this new cohort is about giving the full standard of care to patients. Just as a reminder, the first part of the trial was patients that get chemo induction, then followed by radiation plus NBTXR3.

當我們宣布 FDA 批准了一項增加新隊列的協議修正案時，下一步工作就已經開始了，而這個新隊列將為患者提供全面的標準護理。提醒一下，試驗的第一部分是患者接受化療誘導，然後接受放射治療和 NBTXR3 治療。

Now, that's not the full standard of care that those patients usually receive, as they usually do chemo induction, radiation plus chemo. So in this expansion part, we have added the chemo on the top of radiation plus NBTXR3, and therefore should expect, according to the existing known model of action, a better synergy and even more efficacy than what we've been seeing in the first part of the trial. So this part of the trial is rotating, and we will tell soon when we should expect data on that.

現在，這並不是這些患者通常接受的完整標準護理，因為他們通常會進行化療誘導、放療加化療。因此，在這個擴展部分中，我們在放射治療和 NBTXR3 的基礎上添加了化療，因此根據現有的已知作用模型，我們應該期待比試驗第一部分所見的更好的協同作用和更高的療效。因此，試驗的這一部分正在輪換，我們很快就會告訴您何時可以獲得相關數據。

Thank you. Very helpful.

謝謝。非常有幫助。

Shan Hama, Jefferies.

Shan Hama，傑富瑞。

Hi there. Thank you for taking my question. Just on -- I guess, what portion of costs are you still liable for the NANORAY study, and what are they related to? And how much of it have you been disclosed?

你好呀。感謝您回答我的問題。只是—我想，您仍需承擔 NANORAY 研究的多少費用，這些費用與什麼相關？您透露了多少資訊？

And secondly, I appreciate this might be more of J&J's responsibility, but what's the most recent communication you've had with FDA on the NANORAY program? I think the recent shakeup in the administration and the FDA has caused concerns that some programs might be deprioritized, or there may be sort of delays in meetings. So what have you been hearing? Thank you.

其次，我知道這可能更多的是強生公司的責任，但您最近與 FDA 就 NANORAY 計劃進行了哪些溝通？我認為政府和 FDA 最近的改組引發了人們的擔憂，即某些項目可能會被降低優先級，或者會議可能會延誤。那你聽到了什麼？謝謝。

Thank you. So maybe let me take the second question, then I'll pass the mic to Bart to answer the first one.

謝謝。所以也許讓我來回答第二個問題，然後我會把麥克風交給 Bart 來回答第一個問題。

I mean, we're interacting with FDA or other agencies on different matter, and J&J is doing the same. As our program already are well engaged, we don't have experience, to the best of my knowledge today, any delay in meetings or interaction. So things look normal to date.

我的意思是，我們正在就不同事項與 FDA 或其他機構互動，強生公司也在做同樣的事情。由於我們的專案已經很好地參與其中，據我所知，我們沒有遇到任何會議或互動延遲的情況。到目前為止一切看起來都很正常。

Thank you, Laurent. Happy to follow on. Thank you, Shan, for the question.

謝謝你，洛朗。很高興繼續跟進。謝謝 Shan 提出的問題。

With regards to the remaining costs with Nanobiotix, that is relatively immaterial. As we've guided the public, the vast majority of the costs are now with J&J that has taken over the obligation to fund further to the exchange of milestones that we announced two weeks ago. That may lead to some payments in 2025, 2026, and 2029 that remain on our end, but they're in the single-digit millions in those respective years and are not impacting the cash runway in a meaningful way.

至於 Nanobiotix 的剩餘成本，這相對來說並不重要。正如我們向公眾所引導的那樣，絕大多數成本現在都由強生公司承擔，該公司已承擔了為我們兩週前宣布的里程碑交易提供進一步資金的義務。這可能會導致 2025 年、2026 年和 2029 年的一些付款仍留在我們這邊，但在這些年份，這些付款都只有幾百萬，並且不會對現金流產生重大影響。

We've guided the cash runway to mid-2026, but the removal of the vast majority of this Phase 3 trial cost will benefit us beyond mid-2026, and that burn rate will come down. If one takes a look at our annual R&D expense, of which the majority relates to the NANORAY-312, directly or indirectly, one should expect that we will have a very attractive cost run rate post-mid-2026.

我們已將現金流引導至 2026 年中期，但取消該 3 期試驗的絕大部分成本將使我們在 2026 年中期之後受益，並且燒錢率將會下降。如果看一下我們每年的研發費用，其中大部分直接或間接與 NANORAY-312 相關，那麼我們應該預期，在 2026 年中期之後，我們的成本運行率將非常有吸引力。

Thank you.

謝謝。

Michael Schmidt, Guggenheim Securities.

古根漢證券公司的麥可‧施密特。

Hey, guys. Good morning. I just had a bigger picture question. So now that the NBTRX3 (sic - NBTXR3) program has essentially transitioned fully to J&J operationally and financially, I guess as you think about the company longer term, what are some of the R&D initiatives internally at Nanobiotix that you think could create additional value longer term beyond NBTXR3?

嘿，大家好。早安.我只是想問一個更宏觀的問題。因此，現在 NBTRX3（原文如此 - NBTXR3）專案在營運和財務上已基本完全轉向強生公司，我想當您考慮公司的長期發展時，您認為 Nanobiotix 內部有哪些研發計劃可以在 NBTXR3 之外創造長期的額外價值？

Thanks, Michael, for the question. So maybe first of all, let's say that we're not yet done with NBTXR3. We still have a lot to do. You're fully right when you say that J&J now is taking a good part, a majority, of what is happening with NBTXR3, with the CONVERGE trial, with the transfer of the 312, and so on. But this transfer is not yet done.

謝謝邁克爾提出這個問題。所以首先，我們假設我們還沒有完成 NBTXR3。我們還有很多事情要做。您說強生公司現在在 NBTXR3、CONVERGE 試驗、312 轉移等方面佔據了很大一部分、大部分份額，您說得完全正確。但此次轉移尚未完成。

As we mentioned, it should be in Q3 this year. And there's still a lot to do around the manufacturing, around preclinical, around preparing everything that should go and will go in the dossier for registration. So outside the 312, which is today a big part of the investment in resources of Nanobiotix that now J&J is taking, there's still a lot in parallel. And this, we think, will continue for the coming few years.

正如我們所提到的，它應該在今年第三季。在製造、臨床前以及準備註冊檔案中應該和將要進入的所有內容方面還有很多工作要做。因此，除了 312（目前強生對 Nanobiotix 資源投資的很大一部分）之外，還有很多並行專案。我們認為，這種情況在未來幾年將會持續下去。

Now, it is true that this shift of the 312 is also opening some doors for us, not only because we are going to spend less money, but also we can free some resources to continue to work on our other platform, and mainly the Curadigm platform, which is the platform we want to push after NBTXR3, which is a very broad, applicable platform, not only to potential early deal and partnership, but also to develop our new internal pipeline. But we expect to give more detail on that before the end of this year.

現在，312 的轉變確實也為我們打開了一些大門，不僅因為我們將花費更少的錢，而且我們還可以釋放一些資源來繼續開發我們的其他平台，主要是 Curadigm 平台，這是我們想要在 NBTXR3 之後推動的平台，它是一個非常廣泛、適用的平台，不僅適用於潛在的早期交易和合作夥伴關係，也適用於我們新關係的內部管道。但我們預計在今年年底前提供更多細節。

And so I think you mentioned earlier, but how much additional R&D spend in 2025 and 2026 will be on NBTXR3 versus other programs?

所以我想您之前提到過，但是與其他項目相比，2025 年和 2026 年 NBTXR3 上的額外研發支出是多少？

Bart, do you want to take that one?

巴特，你想拿那個嗎？

Yes, I was unmuting. So what will remain essentially is the 1100 study, MD Anderson, preclinical and discovery work, as well as Curadigm. Each of those are single-digit millions, so the burn will come down quite significantly on the R&D side with the 2012 study making up the majority of the R&D spend. So that is millions per quarter less.

是的，我取消了靜音。因此，基本上剩下的是 1100 項研究、MD Anderson、臨床前和發現工作以及 Curadigm。每項研究的投入都是數百萬，因此研發方面的投入將大幅下降，而 2012 年的研究將佔研發支出的大部分。因此每季就會減少數百萬美元。

The beauty of the Curadigm program is that, as explained to the market, it's a platform that can be partnered, whether it's with existing new drugs or drugs that have failed. So we expect that the burn will be very efficient in that regard. It will go up versus what it is now, but it will, on a net basis, with the removal of the Phase 3 liability, be significantly less on a net basis going forward.

Curadigm 計畫的優點在於，正如向市場解釋的那樣，它是一個可以合作的平台，無論是與現有的新藥還是已經失敗的藥物合作。因此我們預期燃燒在這方面會非常有效。與現在相比，它會上升，但從淨額來看，隨著第三階段責任的取消，未來的淨額將會大幅減少。

Thank you.

謝謝。

Swayampakula, Ramakanth; HCW.

Swayampakula，Ramakanth；HCW。

Thank you. This is RK from H.C. Wainwright. Good afternoon, Laurent and Bart. So a couple of quick questions here.

謝謝。這是來自 H.C. Wainwright 的 RK。下午好，Laurent 和 Bart。這裡有幾個簡單的問題。

So this is for Bart. You were talking about the runway which currently stands until mid-2026, and you were also saying there are potential ways for you to extend it into '27. So what could be the potential non-dilutive ways? And also, how much of a gap is there for you to fill so that you can take it up to 2027 or into 2027 from where it stands currently?

這是給巴特的。您談到了目前將持續到 2026 年中期的跑道，並且您還說有可能將其延長到 2027 年。那麼潛在的非稀釋性方法有哪些呢？此外，您需要填補多少差距才能將其提升到 2027 年或從目前的水平進入 2027 年？

Thank you, RK. So we feel that the enterprise value is significantly disconnected with the market cap. Therefore, dilutive options are not our preference. We have EIB debt in our cap structure, and any more debt, we believe, is not the ideal way to go about things.

謝謝你，RK。因此我們認為企業價值與市值有很大脫節。因此，稀釋性選擇權不是我們的偏好。我們的資本結構中包含歐洲投資銀行債務，我們認為，任何更多的債務都不是理想的處理方式。

But other non-dilutive financing options, such as royalty financing, we believe hold good promise for the company, given the type of asset this is. Just to remind, it's a very versatile asset. Laurent mentioned it in the call. It's tumor agnostic, combination agnostic, target agnostic. We see significant engagement and investment by our partner, J&J. We expect that to continue. So it is a very interesting asset for many of the providers in that space.

但考慮到這種資產類型，我們認為其他非稀釋性融資選擇（例如特許權使用費融資）對公司來說前景良好。需要提醒的是，它是一種用途非常廣泛的資產。勞倫特在通話中提到了這一點。它與腫瘤、組合和目標無關。我們看到我們的合作夥伴強生公司投入了大量的精力和資金。我們預計這種情況將會持續下去。因此，對於該領域的許多提供者來說，這是一項非常有趣的資產。

As our burn will come down quite significantly, we don't need a lot of money. It would be low teens to get into 2027. It just behooves us at this point in time to remove the finance overhang and get into a safe harbor, because there's tremendous value in this asset that needs to result in value creation for our shareholders. And we want to make sure that we do that so that there's no finance overhang and people can just appreciate the technology, the versatility of it, that is partnered with a partner that we believe is an ideal partner for this asset and bring it, hopefully, in many indications should data readouts be positive.

由於我們的資金消耗將大幅下降，因此我們不需要太多的錢。到 2027 年，這一數字將低於 10%。此時此刻，我們理應消除財務負擔，進入安全港，因為這項資產具有巨大的價值，需要為我們的股東創造價值。我們希望確保我們做到這一點，這樣就不會出現財務負擔，人們就可以欣賞這項技術及其多功能性，與我們認為是這項資產的理想合作夥伴合作，並希望在許多跡象表明數據讀數是積極的。

Thank you for that, Bart. And then, Laurent, just thinking about R3 for a second. Having seen the data that we have seen so far, both on the safety side and on the efficacy side, to me, there doesn't seem a real reason why this should not get into the market, granted it may take a little bit of time, but there's no reason to think that it should not get to the market.

謝謝你，巴特。然後，Laurent，請想想 R3。從我們目前所看到的安全性和有效性數據來看，對我來說，似乎沒有理由不將其推向市場，雖然這可能需要一點時間，但沒有理由認為它不應該進入市場。

However, what could be potentially the reasons why it cannot get to the market? I was just thinking about it, because based on what we know about the molecule, I feel quite confident. But other than the timing part of it, are there any other things that I'm being blindsided?

然而，它無法進入市場的潛在原因可能是什麼？我只是在想這件事，因為基於我們對該分子的了解，我感到非常有信心。但除了時間上的問題之外，還有其他事情讓我措手不及嗎？

Well, thank you, RK, for the $10 billion question. Well, I think we could have had a different answer to this question, depending on timing, you would ask for it. In the past, we would have indicated manufacturing is always a risk. Getting some first randomized data is always a risk until you have them. Not having a partner to market the product or to make sure we can develop broadly would have been a risk, and many other things.

好吧，RK，謝謝你提出這個價值 100 億美元的問題。嗯，我認為我們可以對這個問題有不同的答案，這取決於時間，你會問這個問題。過去，我們會指出製造業始終存在風險。在獲得一些初始隨機資料之前，獲取它們始終是有風險的。如果沒有合作夥伴來行銷產品或確保我們能夠廣泛發展，那將是一個風險，並且將面臨許多其他風險。

But I think where we stand now, I think all those usual, big, impactful risks that the biotech is facing are behind us. So I will say that we are in a very derisked situation right now. There's never 100% guarantee in any of the things. I think what we should just do is wait. There's not too much time to wait now to get to the next big inflection point and to, on our side, help J&J to move as fast as they can and to bring this product to market.

但我認為，就我們目前的狀況而言，生物技術面臨的所有那些常見的、巨大的、有影響力的風險都已經過去了。所以我想說，我們現在處於一個風險非常低的情況。任何事情都不可能有 100% 的保證。我認為我們應該做的就是等待。現在沒有太多時間等待下一個重大轉折點，從我們的角度來看，我們將幫助強生盡快採取行動，將產品推向市場。

Thank you for that. And then the last question from me is also on the Curadigm asset. Probably I've asked this question in the past. What's the gating event that needs to get done so that you can initiate a clinical program? Is it resources, or is it time in the sense of getting all the material together to start a program?

謝謝你。我的最後一個問題也是關於 Curadigm 資產的。我可能以前問過這個問題。為了啟動臨床計劃，需要完成哪些門控事件？它是資源，還是將所有材料整合在一起以啟動程序的時間？

Well, I think it's essentially timing. We have enough resources to push this program. As Bart mentioned, at the stage of development, it does not cost a lot of money. But also, as we want to re-emphasize the partnership activity on that, then there probably will be a big part of it that will be done on other times.

嗯，我認為這本質上就是時機問題。我們有足夠的資源來推動這項計劃。正如巴特所提到的，在開發階段，它並不需要花費很多錢。但同時，由於我們想再次強調這方面的合作活動，因此其中很大一部分工作可能會在其他時間完成。

So we're working on our internal pipeline and also have been starting interacting with many biotech and pharma. We have a good number of MTAs already signed and on their way. So things are moving, and we hope -- I will give much more info by the end of this year.

因此，我們正在致力於內部管道建設，並且已經開始與許多生物技術和製藥公司進行互動。我們已經簽署了大量 MTA，並且正在準備中。事情正在進展中，我們希望——我將在今年年底前提供更多資訊。

Thank you. Thanks for taking all my questions.

謝謝。感謝您回答我的所有問題。

(Operator Instructions) Eric Musonza, UBS.

（操作員說明）Eric Musonza，UBS。

Actually, this is David Dai from UBS. So yeah, just actually two questions for me as well. So regarding the NANORAY-312 file, so you're planning to enroll patients with and without cetuximab. These patients who receive cetuximab will likely have a longer survival. Could you help us understand what percentage of patients are going to be enrolled with cetuximab and what percentage will not have cetuximab? And just curious if there's going to be a cap in terms of patients who are -- who have the cetuximab background.

事實上，我是瑞銀的大衛‧戴 (David Dai)。是的，實際上我也有兩個問題。關於 NANORAY-312 文件，您計劃招募使用和未使用西妥昔單抗的患者。接受西妥昔單抗治療的患者可能會有更長的生存期。您能否幫助我們了解有多少比例的患者將接受西妥昔單抗治療，有多少比例的患者不會接受西妥昔單抗治療？我只是好奇，對於有西妥昔單抗背景的患者，是否會有限制。

Thanks, David.

謝謝，大衛。

So cetuximab is not the biggest used drug in head and neck when it comes to frail and elderly patients. Nevertheless, that's something that is in the standard healthcare guideline. But when you look at it, not many people are using cetuximab. The reason why this drug has been added is because they are in the guidelines. So we need to leave the choice open for physician to use it or not. So that's one. And in order to make sure that the trial is balanced and there is no bias, we've made cetuximab use as a stratification factor. So we should assume a balanced number of patients getting it in both arms.

因此，對於體弱和老年患者來說，西妥昔單抗並不是頭頸部最常用的藥物。儘管如此，這就是標準醫療保健指南中的內容。但如果你看一下，你會發現使用西妥昔單抗的人並不多。之所以添加這種藥物，是因為它們在指南中。因此，我們需要讓醫生自行選擇是否使用它。這就是其中之一。為了確保試驗的平衡性且沒有偏見，我們將西妥昔單抗的使用作為分層因子。因此，我們應該假設接受兩種療法的患者數量是平衡的。

Now, why cetuximab is not used that much in those patients is because when you look at the detail of the Bonner paper, what you see is that for elderly people, the cetuximab use is detrimental versus radiation alone. So of course, looking at the overall data, you see a benefit for cetuximab, but this benefit is exclusively driven by younger patients.

現在，為什麼西妥昔單抗在這些患者中沒有被廣泛使用，是因為當你查看 Bonner 論文的細節時，你會發現對於老年人來說，使用西妥昔單抗比單獨使用放射治療更有害。因此，當然，從整體數據來看，你會看到西妥昔單抗的益處，但這種益處完全是由年輕患者帶來的。

So at the end of the day, we think that cetuximab in this trial will have either a neutral effect; we should not expect more efficacy coming from it, or a plus, a little plus. But if there is some small benefit, we should assume that this benefit will be at the minimum equal in the arm with NBTXR3 or better if we anticipate synergies. So that's why we don't think cetuximab in this trial will play a key role.

所以最終，我們認為西妥昔單抗在本次試驗中要不是具有中性效果；我們不應該期望它能帶來更多的療效，就是有一點好處。但如果有一些小的好處，我們應該假設這種好處至少與 NBTXR3 相同，或者如果我們預期有協同作用的話會更好。所以這就是為什麼我們認為西妥昔單抗在這次試驗中不會發揮關鍵作用。

That's really helpful. And then there's another question on the upcoming data readout. There are many updates in 2025, including the baseline data from the relapse metastatic and neck cancer in combination with PD-1. Can you just share with us mechanistically how do you think R3 will be additive to PD-1 to exert better systemic benefit for those metastatic patients?

這真的很有幫助。然後還有關於即將公佈的數據的另一個問題。2025年有許多更新，包括與PD-1合併治療復發轉移性癌症和頸癌的基線數據。您能否從機制上與我們分享一下，您認為 R3 將如何與 PD-1 結合，為轉移性患者帶來更好的系統性益處？

Sure. First of all, before getting to the benefit of systemic activity of NBTXR3, just want to remind that for all patients getting PD-1, the first time they will get PD-1, they're usually one-third of those patients that are only locally relapsed, one-third that will have local relapse plus met, and a third only will have met only. And most of the patients, the 60% I mentioned previously and beyond, they're coming from the failure of previous lines of treatment. So before getting into any systemic activity of NBTXR3, we should just remind that those patients getting PD-1, they also need, and primarily need, a local control.

當然。首先，在了解 NBTXR3 的系統性活性益處之前，只想提醒一下，對於所有接受 PD-1 治療的患者，第一次接受 PD-1 治療的患者中，通常有三分之一的患者僅出現局部復發，三分之一的患者出現局部復發加轉移，還有三分之一的患者僅出現轉移。大多數的患者，也就是我之前提到的 60% 以上的患者，都是因為先前治療方法失敗而生病的。因此，在了解 NBTXR3 的任何系統性活動之前，我們應該提醒那些接受 PD-1 治療的患者，他們也需要，而且主要需要局部控制。

That's what our PIs are mentioning quite repeatedly when we talk to them, that systemic control in head and neck metastatic patients or locally relapsed plus met is good but usually does not translate into direct link to PFS and overall survival. There's always this need and an important need to control the local tumor, and that's where we know NBTXR3 could play a key role first. So even if we don't look at the systemic effect, we have a strong potential to improve outcome for patient just based on local control.

這就是我們在與 PI 交談時反覆提到的，頭頸部轉移性患者或局部復發加轉移患者的全身控制效果良好，但通常不會轉化為與 PFS 和整體存活率的直接關聯。總是存在這種需求，而且是控制局部腫瘤的重要需求，而這正是我們知道 NBTXR3 可以首先發揮關鍵作用的地方。因此，即使我們不考慮系統性影響，我們也有很強的潛力僅基於局部控制來改善患者的治療結果。

Now, when it comes to systemic, we've been proven in multiple studies with MD Anderson that when we combine R3 to radiation versus radiation alone, we can trigger a much deeper systemic immune response with different mechanism, and this has been fully extended study in preclinical model by James Welsh. So what we start seeing, and that's part of what we would like to show in the next set of data we will explore for the 1100, is really those two things, local control and systemic control. And we clearly see that the magnitude of effect we see cannot just be linked to local control, not to what extent we have the systemic control. That's something we are exploring.

現在，說到系統性，我們已經在與 MD Anderson 合作的多項研究中證明，當我們將 R3 與放射治療相結合而不是單獨使用放射治療時，我們可以以不同的機制觸發更深層次的系統性免疫反應，並且這已由 James Welsh 在臨床前模型中進行了全面擴展的研究。因此，我們開始看到的，也是我們希望在下一組針對 1100 進行探索的數據中展示的部分，實際上是這兩件事，即局部控制和系統控制。我們清楚地看到，我們看到的影響程度不能僅僅與局部控制有關，而與我們擁有的系統控製程度無關。這是我們正在探索的事情。

That's really helpful. Thank you so much, and congrats on the progress.

這真的很有幫助。非常感謝，並祝賀你的進展。

There are no further questions at this time. I would like to hand the call over to Dr. Levy for his closing remarks.

目前沒有其他問題。我想把電話交給 Levy 博士，請他做最後發言。

Thank you. Listen, thank you, everyone. It was another fruitful conversation. We'll have plenty of news to deliver this year, so we're going to go back to work and prepare that for you.

謝謝。聽著，謝謝大家。這是又一次富有成果的對話。今年我們將會有許多新聞要發布，所以我們將回去工作並為您做好準備。

Thank you for your attention, and we wish you a very good day, and let's talk soon.

感謝您的關注，祝您有個愉快的一天，我們很快再聊。

Ladies and gentlemen, this concludes today's conference -- today's presentation. Thank you once again for your participation. You may now disconnect your lines. Thank you, and have a great day.

女士們、先生們，今天的會議——今天的演講到此結束。再次感謝您的參與。現在您可以斷開線路了。謝謝您，祝您有愉快的一天。